Literature DB >> 22520477

Low p53 binding protein 1 (53BP1) expression is associated with increased local recurrence in breast cancer patients treated with breast-conserving surgery and radiotherapy.

Hanmanth J R Neboori1, Bruce G Haffty, Hao Wu, Qifeng Yang, Amal Aly, Sharad Goyal, Devora Schiff, Meena S Moran, Ryan Golhar, Chunxia Chen, Dirk Moore, Shridar Ganesan.   

Abstract

PURPOSE: To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT). METHODS AND MATERIALS: A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log-rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence-free survival (IBRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS).
RESULTS: Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014).
CONCLUSION: Our data indicate that low 53BP1 expression is an independent prognostic indicator for local relapse among other endpoints in early-stage breast cancer and TN breast cancer patients treated with BCS+RT. These results should be verified in larger cohorts of patients to validate their clinical significance.
Copyright © 2012 Elsevier Inc. All rights reserved.

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Year:  2012        PMID: 22520477     DOI: 10.1016/j.ijrobp.2012.01.089

Source DB:  PubMed          Journal:  Int J Radiat Oncol Biol Phys        ISSN: 0360-3016            Impact factor:   7.038


  19 in total

1.  Expression of DNA damage checkpoint 53BP1 is correlated with prognosis, cell proliferation and apoptosis in colorectal cancer.

Authors:  Jianping Bi; Ai Huang; Tao Liu; Tao Zhang; Hong Ma
Journal:  Int J Clin Exp Pathol       Date:  2015-06-01

2.  53BP1 is limiting for NHEJ repair in ATM-deficient model systems that are subjected to oncogenic stress or radiation.

Authors:  Ivana Rybanska-Spaeder; Taylor L Reynolds; Jeremy Chou; Mansi Prakash; Tameca Jefferson; David L Huso; Stephen Desiderio; Sonia Franco
Journal:  Mol Cancer Res       Date:  2013-07-15       Impact factor: 5.852

3.  UbcH7 regulates 53BP1 stability and DSB repair.

Authors:  Xiangzi Han; Lei Zhang; Jinsil Chung; Franklin Mayca Pozo; Amanda Tran; Darcie D Seachrist; James W Jacobberger; Ruth A Keri; Hannah Gilmore; Youwei Zhang
Journal:  Proc Natl Acad Sci U S A       Date:  2014-11-24       Impact factor: 11.205

4.  53BP1 loss induces chemoresistance of colorectal cancer cells to 5-fluorouracil by inhibiting the ATM-CHK2-P53 pathway.

Authors:  Jing Yao; Ai Huang; Xiumei Zheng; Tao Liu; Zhenyu Lin; Sheng Zhang; Qin Yang; Tao Zhang; Hong Ma
Journal:  J Cancer Res Clin Oncol       Date:  2016-11-12       Impact factor: 4.553

5.  Regulatory cross-talk determines the cellular levels of 53BP1 protein, a critical factor in DNA repair.

Authors:  Franklin Mayca Pozo; Jinshan Tang; Kristen W Bonk; Ruth A Keri; Xinsheng Yao; Youwei Zhang
Journal:  J Biol Chem       Date:  2017-03-02       Impact factor: 5.157

Review 6.  BRCA1 Mutation: A Predictive Marker for Radiation Therapy?

Authors:  Charlene Kan; Junran Zhang
Journal:  Int J Radiat Oncol Biol Phys       Date:  2015-10-01       Impact factor: 7.038

7.  Inferring Cell Subtypes and LncRNA Function by a Cell-Specific CeRNA Network in Breast Cancer.

Authors:  Xin Chen; Jing Xu; Feng Zeng; Chao Yang; Weijun Sun; Tao Yu; Haokun Zhang; Yan Li
Journal:  Front Oncol       Date:  2021-04-27       Impact factor: 6.244

8.  Novel Integrative Genomics Approach for Associating GWAS Information with Intrinsic Subtypes of Breast Cancer.

Authors:  Chindo Hicks; Tejaswi Koganti; Alexandra S Brown; Jesus Monico; Kandis Backus; Lucio Miele
Journal:  Cancer Inform       Date:  2013-05-15

9.  53BP1 expression is a modifier of the prognostic value of lymph node ratio and CA 19-9 in pancreatic adenocarcinoma.

Authors:  Natalie L Ausborn; Tong Wang; Sabrina C Wentz; Mary Kay Washington; Nipun B Merchant; Zhiguo Zhao; Yu Shyr; Anuradha Bapsi Chakravarthy; Fen Xia
Journal:  BMC Cancer       Date:  2013-03-26       Impact factor: 4.430

10.  53BP1 sensitizes breast cancer cells to 5-fluorouracil.

Authors:  Xiaoyan Li; Xiaoli Kong; Xiangnan Kong; Yang Wang; Shi Yan; Qifeng Yang
Journal:  PLoS One       Date:  2013-09-06       Impact factor: 3.240

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